The movement of fluid and solute between the vascular, interstitial, cellular and alveolar compartments in response to hydrostatic pressure and osmotic alterations in the pulmonary circulation is under study in isolated perfused and weight monitored lungs and in the intact anesthetized dog. In addition, the effects of agents known to produce pulmonary edema or cell injury (ethchlorvynol, alloxan, alpha naphthyl thiourea, oleic acid, paraquats) are being investigated. The fluid and solute movements are quantified by nonequilibrium thermodynamics in terms of four coefficients relating fluxes to driving forces across the endothelial and epithelial barriers: filtration coefficient of volumetric flow, and permeability, osmotic reflection and solvent drag reflection coefficients of the solute with respect to the barrier. These coefficients will be determined for a variety of ions and neutral molecules with varied oil:water distribution coefficients. The effect of decreased temperature (which decreases permeability and reflection coefficients of lipophilic molecules) on gas exchanges will be determined. Mathematical modeling of the postulated parallel pathway system of transport and exchange will be carried out. The modifiability of the barrier characteristics will be correlated with anatomical changes as determined by morphometry and stereology by visible light and electron microscopy. The metabolic and transport activities of the intact barriers and of the individual cellular constituents will be studied both in vivo, in vitro in isolated perfused systems, in isolated and in cultured cells. The factors determining the appearance of pulmonary edema in the isolated perfused preparation will be investigated and the hypothesis tested that small solutes as well as the conventional Starling factors play a role in the control of the extravascular lung water.